Interplay between genetics and lifestyle on pain susceptibility in women with fibromyalgia: the al-Ándalus project

This work was supported by the Spanish Ministry of Economy and Competitiveness (I + D+i DEP2010-15639, I + D+i DEP2013-40908-R to M.D.-F.; BES-2014-067612 to F.E.-L.), the Spanish Ministry of Education (FPU13/03410 to D.S.-T.; FPU15/0002 to B.G.-C.), the Consejeria de Turismo, Comercio y Deporte, Junta de Andalucia (CTCD-201000019242-TRA to M.D.-F.), the Consejeria de Salud, Junta de Andalucia (PI-0520-2016 to M.D.-F.) and the University of Granada, Plan Propio de Investigacion 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES). The funders of the present study did not have any role in the study design, data collection and analyses, decision to publish or preparation of the manuscript.Objectives. It is widely acknowledged that the experience of pain is promoted by both genetic susceptibility and environmental factors such as engaging in physical activity (PA), and that pain-related cognitions are also important. Thus, the purpose of the present study was to test the association of 64 polymorphisms (34 candidate genes) and the gene–gene, gene–PA and gene–sedentary behaviour interactions with pain and pain-related cognitions in women with FM. Methods. Saliva samples from 274 women with FM [mean (S.D.) age 51.7 (7.7) years] were collected for extracting DNA. We measured PA and sedentary behaviour by accelerometers for a week, pain with algometry and questionnaires, and pain-related cognitions with questionnaires. To assess the robustness of the results, a meta-analysis was also performed. Results. The rs6311 and rs6313 polymorphisms (5-hydroxytryptamine receptor 2A, HTR2A) were individually related to algometer scores. The interaction of rs4818 (catechol-O-methyltransferase, COMT) and rs1799971 (opioid receptor l gene, OPRM1) was related to pain catastrophizing. Five gene–behaviour interactions were significant: the interactions of sedentary behaviour with rs1383914 (adrenoceptor alpha 1A, ADRA1A), rs6860 (charged multivesicular body protein 1A, CHMP1A), rs4680 (COMT), rs165599 (COMT) and rs12994338 (SCN9A) on bodily pain subscale of the Short Form 36. Furthermore, the meta-analysis showed an association between rs4680 (COMT) and severity of FM symptoms (codominant model, P-value 0.032). Conclusion. The HTR2A gene (individually), COMT and OPRM1 gene–gene interaction, and the interactions of sedentary behaviour with ADRA1A, CHMP1A, COMT and SCN9A genes were associated with pain-related outcomes. Collectively, findings from the present study indicate a modest contribution of genetics and gene– sedentary behaviour interaction to pain and pain catastrophizing in women with FM. Future research should examine whether reducing sedentary behaviour is particularly beneficial for reducing pain in women with genetic susceptibility to pain.Spanish Government I + D+i DEP2010-15639 I + D+i DEP2013-40908-R BES-2014-067612 FPU13/03410 FPU15/0002Junta de Andalucia CTCD-201000019242-TRA PI-0520-2016University of Granada, Plan Propio de InvestigacionUnit of Excellence on Exercise and Health (UCEES